Open Access Research article

Estrogen protects against the synergistic toxicity by HIV proteins, methamphetamine and cocaine

Jadwiga Turchan12, Caroline Anderson12, Kurt F Hauser3, Qinmiao Sun12, Jiayou Zhang2, Ying Liu4, Phyllis M Wise4, Inna Kruman5, William Maragos13, Mark P Mattson5, Rosemarie Booze3 and Avindra Nath12*

Author Affiliations

1 Department of Neurology, University of Kentucky, Lexington KYl, USA

2 Department of Microbiology and Immunology, University of Kentucky, Lexington KYl, USA

3 Department of Anatomy and Neurobiology, University of Kentucky, Lexington KYl, USA

4 Department of Physiology, University of Kentucky, Lexington KY, USA

5 Laboratory of Neurosciences, National Institute on Aging, Baltimore, MD, USA

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BMC Neuroscience 2001, 2:3  doi:10.1186/1471-2202-2-3

Published: 2 March 2001

Abstract

Background

Human immunodeficiency virus (HIV) infection continues to increase at alarming rates in drug abusers, especially in women. Drugs of abuse can cause long-lasting damage to the brain and HIV infection frequently leads to a dementing illness.To determine how these drugs interact with HIV to cause CNS damage, we used an in vitro human neuronal culture characterized for the presence of dopaminergic receptors, transporters and estrogen receptors. We determined the combined effects of dopaminergic drugs, methamphetamine, or cocaine with neurotoxic HIV proteins, gp120 and Tat.

Results

Acute exposure to these substances resulted in synergistic neurotoxic responses as measured by changes in mitochondrial membrane potential and neuronal cell death. Neurotoxicity occurred in a sub-population of neurons. Importantly, the presence of 17beta-estradiol prevented these synergistic neurotoxicities and the neuroprotective effects were partly mediated by estrogen receptors.

Conclusion

Our observations suggest that methamphetamine and cocaine may affect the course of HIV dementia, and additionally suggest that estrogens modify the HIV-drug interactions.